The 2-oxo acid dehydrogenase multienzyme complexes are enormous macromolecular assemblies (Mw 4-10 million Da). The main enzymes, each present in multiple copies, are called E1, E2 and E3. Structures of E2 and E3 from different sources have been determined but no structural information is available for the E1 component which is the most important protein in terms of regulation and from medical perspective. The main goal of the work of concern in this proposal is structure determination of B. stearothermophilus E1p in complex with E2 didomain (170 kDa), P. putida E1b (160 kDa) and rat E1 kinase (170 kDa)